Sunday, September 30, 2012

More on Nanoparticles causing DNA damage from MOM hips through oxidatve stress (5 of x in a series)

Prior posts in the sequence
1 of x
More on Nanoparticles causing DNA damage from MOM hips with oxidative stress ( 1 of x in a series)
2 of x
3 of x
4 of x

Discussing the 2nd of 4 seminal works on the issues related to causing free radicals in the cell environment from MoM:  Nanonparticles can cause DNA damage across a cellular barrier.

The last post in this series established that the group of scientists demonstrated there is both cytotoxic and genotoxic  effects of nanoparticles of cobalt chrom alloy in a tissue culture using human fibroblasts.  /The research on that article was done in 2007.

This article was published in 2009 and goes a step further to show that the nanoparticles can damage human fibroblast cells across the cell barrier without having to cross the barrier.  these would be categorized as indirect effects when evaluating the safety of nanoparticles in the body. 

1.  Nanoparticles have led to increasing concerns about their potential toxicity in the body.

2.  the current lack of knowledge in this regard has led to an urgent call for the establishment of principles and test procedures to ensure the safe manufacturing  and use of nanoparticles [
which are by products of the metal on metal hips.]

3.  Humans are exposed internally to CoCr nanoparticle by wear mechanisms associated with MoM chromium and Cobalt particles which are known to have both genotoxic and cytotoxic effects in human tissue culture causing DNA damage, chromosome aberrations and cell death if they are applied above a certain threshold.

4.  This paper study has been undertaken to assess the cellular toxicity when located on the other side of a fully confluent cell barrier.

5.  This study used:
  •  BeWo cells which is a human placental choriocarcinoma cell line
  • Trophoblasts  which are specialised cells of the placenta that play an important role in embryo implantation and interaction with the decidualised maternal uterus
6.  Indirect exposure for 24 hours of human fibroblasts to Co and Cr nanoparticles were internalized by these BeWo cells and did not traverse the cell barrier as they were too large to pass through but nonetheless  caused significant DNA damage to the fibroblasts.

7.  Mass spectroscopic analyses revealed the presence of low concentrations of co and cr ions indicating that metal ions were able to cross the cell barrier after particle exposure

8.   Direct nanoparticle toxicity to DNA is thought to be caused by oxidative damage including that from free radicals generated from the reactive particle surfaces and by the creation of chemical DNA adducts.

9.  The outcome of the indirect exposure, increase in tatraploidy* and DNA damage without overall change in cell proliferation is different from that of the direct exposure to nanoparticles at the same dose.

*tetraploid /tet·ra·ploid/ (tet´rah-ploid). 1. characterized by tetraploidy. 2. an individual or cell having four sets of chromosomes.  tetraploidy  is observed in 1–2% of early miscarriages

10  They suggested that a mechanism for the indirect manner in which the top layer of the BeWo cell barrier is damaged  might be through:
  • nano particle damage to the mitochondria
  • hypoxic mimicking actions of the cobalt ions or 
  • mechanical stress to certain mechanosensitve channels which in turn triggers cell signalling and secondary messengers 
11.  This mechanism works in similar way to that proposed to radiation by stander effect.  ---that is, cells exposed to low-dose radiation send a signal to non-irradiated cells, causing an induction of chromosome and gene mutations in the mitochondrial DNA through this signal.

12.  In this context, it is feasible that a process of indirect DNA damage  might have relevance to the human placenta because  it is in the first trimester that the embryo may be particularly vulnerable to teratogenic effects.

[ I have published other journal articles on similar topics:
13.  Tetratploidy as seen in these experiments can be associated with malformation[ in the fetus]!

14.  Extra-embrionic pathways have been suggested to modulate reactive oxygen species (ROS).  Excess free iron in the fetus, as tranported across the placenta by transferrin also contributes to oxidative stress which may damage fetal organs as apart of oxygen free radical disease of neonatology.

Conclusion:  The investigators concluded that an evaluation of nanoparticle safety not be limited to whether they gain access to privileged sites.  Instead, there should be an evaluation of their genotoxic potential for both direct and indirect effects to avoid any potential toxic risks to targets on the distal side of the cell barrier.


Information in the brackets are added by Connie: []

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